The existence of nicotinic-cholinergic receptors in the central nervous system of the rat will be studied by determining the effect of nicotine on the release of dopamine and serotonin from superfused slices and synaptosomes and by measuring the specific binding of the ligand alpha-bungarotoxin in the striatum and hypothalamus. The pre- and post-synaptic location of these receptors will be determined by a combination of using pre-synaptic markers and specific lesioning studies such as the neurotoxins 6-hydroxydopamine, kainic acid or electrical and surgical lesions of various pathways. Physiological function will be studied by determining the effect of nicotinic activation on the spontaneous and induced release of the two neurotransmitters. Of particular importance will be the determination of whether or not the response to nicotinic receptors or actual number of receptors is increased or decreased following procedures which interfere with cholinergic neurotransmission, following chronic nicotinic administration or blockade of the nicotinic receptors. These latter observations are of great relevance since they present a more valid means of correlating the effect of nicotine on the nervous system as it relates to tobacco smoking and its abuse. The present study will provide valuable information on whether the use of centrally acting drugs which modify neurotransmission may result in changes in the sensitivity of nicotine receptors.